Entada phaseoloides (L.) Merr. is an important traditional medicinal plant. The stem of Entada phaseoloides is popularly used as traditional medicine because of its significance in dispelling wind ...and dampness and remarkable anti-inflammatory activities. Triterpenoid saponins are the major bioactive compounds of Entada phaseoloides. However, genomic or transcriptomic technologies have not been used to study the triterpenoid saponin biosynthetic pathway in this plant.
We performed comparative transcriptome analysis of the root, stem, and leaf tissues of Entada phaseoloides with three independent biological replicates and obtained a total of 53.26 Gb clean data and 116,910 unigenes, with an average N50 length of 1218 bp. Putative functions could be annotated to 42,191 unigenes (36.1%) based on BLASTx searches against the Non-redundant, Uniprot, KEGG, Pfam, GO, KEGG and COG databases. Most of the unigenes related to triterpenoid saponin backbone biosynthesis were specifically upregulated in the stem. A total of 26 cytochrome P450 and 17 uridine diphosphate glycosyltransferase candidate genes related to triterpenoid saponin biosynthesis were identified. The differential expressions of selected genes were further verified by qPT-PCR.
The dataset reported here will facilitate the research about the functional genomics of triterpenoid saponin biosynthesis and genetic engineering of Entada phaseoloides.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
stem is known for its high medicinal benefits and
value. Flavonoids are one of the
in
stem. However, the regulatory mechanism of flavonoids accumulation in
is lacking. Here, phytochemical compounds ...and transcripts from stems at different developmental stages in
were investigated by metabolome and transcriptome analysis. The metabolite profiling of the oldest stem was obviously different from young and older stem tissues. A total of 198 flavonoids were detected, and flavones, flavonols, anthocyanins, isoflavones, and flavanones were the main subclasses. The metabolome data showed that the content of acacetin was significantly higher in the young stem and older stem than the oldest stem. Rutin and myricitrin showed significantly higher levels in the oldest stem. A total of 143 MYBs and 143 bHLHs were identified and classified in the RNA-seq data. Meanwhile, 34 flavonoid biosynthesis structural genes were identified. Based on the expression pattern of structural genes involved in flavonoid biosynthesis, it indicated that flavonol, anthocyanin, and proanthocyanin biosynthesis were first active during the development of
stem, and the anthocyanin or proanthocyanin biosynthesis branch was dominant; the flavone biosynthesis branch was active at the late developmental stage of the stem. Through the correlation analysis of transcriptome and metabolome data, the potential candidate genes related to regulating flavonoid synthesis and transport were identified. Among them, the MYBs, bHLH, and TTG1 are coregulated biosynthesis of flavonols and structural genes, bHLH and transporter genes are coregulated biosynthesis of anthocyanins. In addition, the WDR gene TTG1-like (AN11) may regulate dihydrochalcones and flavonol biosynthesis in specific combinations with IIIb bHLH and R2R3-MYB proteins. Furthermore, the transport gene protein TRANSPARENT TESTA 12-like gene is positively regulated the accumulation of rutin, and the homolog of ABC transporter B family member gene is positively correlated with the content of flavone acacetin. This study offered candidate genes involved in flavonoid biosynthesis, information of flavonoid composition and characteristics of flavonoids accumulation, improved our understanding of the MYBs and bHLHs-related regulation networks of flavonoid biosynthesis in
stem, and provided references for the metabolic engineering of flavonoid biosynthesis in
stem.
Although both persistent itch and inflammation are commonly associated with allergic contact dermatitis (ACD), it is not known if they are mediated by shared or distinct signaling pathways. Here we ...show that both TRPA1 and TRPV1 channels are required for generating spontaneous scratching in a mouse model of ACD induced by squaric acid dibutylester (SADBE), a small molecule hapten, through directly promoting the excitability of pruriceptors. TRPV1 but not TRPA1 channels protect the skin inflammation, as genetic ablation of TRPV1 function or pharmacological ablation of TRPV1-positive sensory nerves promotes cutaneous inflammation in the SADBE-induced ACD. Our results demonstrate that persistent itch and inflammation are mediated by distinct cellular and molecular mechanisms in a mouse model of ACD. Identification of distinct roles of TRPA1 and TRPV1 in regulating itch and inflammation may provide new insights into the pathophysiology and treatment of chronic itch and inflammation in ACD patients.
Medicinal plants produce important substrates for their adaptation and defenses against environmental factors and, at the same time, are used for traditional medicine and industrial additives. Plants ...have relatively little in the way of secondary metabolites via biosynthesis. Recently, the whole-genome sequencing of medicinal plants and the identification of secondary metabolite production were revolutionized by the rapid development and cheap cost of sequencing technology. Advances in functional genomics, such as transcriptomics, proteomics, and metabolomics, pave the way for discoveries in secondary metabolites and related key genes. The multi-omics approaches can offer tremendous insight into the variety, distribution, and development of biosynthetic gene clusters (BGCs). Although many reviews have reported on the plant and medicinal plant genome, chemistry, and pharmacology, there is no review giving a comprehensive report about the medicinal plant genome and multi-omics approaches to study the biosynthesis pathway of secondary metabolites. Here, we introduce the medicinal plant genome and the application of multi-omics tools for identifying genes related to the biosynthesis pathway of secondary metabolites. Moreover, we explore comparative genomics and polyploidy for gene family analysis in medicinal plants. This study promotes medicinal plant genomics, which contributes to the biosynthesis and screening of plant substrates and plant-based drugs and prompts the research efficiency of traditional medicine.
Gymnadenia conopsea (L.) R. Br. is an important perennial terrestrial photosynthetic orchid species whose microbiomes are considered to play an important role in helping its germination and growth. ...However, the assemblage of G. conopsea root-associated microbial communities is poorly understood. The compositions of fungal and bacterial communities from the roots and corresponding soil samples in G. conopsea across distinct biogeographical regions from two significantly different altitudes were characterized at the vegetative and reproductive growth stages. The geographical location, developmental stage and compartment were factors contributing to microbiome variation in G. conopsea. Predominant fungal taxa include Ascomycota, Basidiomycota, Mortierellomycota and Chytridiomycota, whereas Proteobacteria, Bacteroidetes, Acidobacteria, Actinobacteria, Verrucomicrobia, Chloroflexi, TM7 and Planctomycetes were predominant bacterial taxa. Using G. conopsea as a model, the structural and functional composition in G. conopsea root-associated microbiomes were comprehensive analyzed. Contrary to previous studies, biogeography was the main factor influencing the microbial community in this study. Besides, compartment and developmental stage should also be considered to analyze the variation of microbiota composition. Although the microbial composition varied greatly by location, the symbiotic microorganisms of G. conopsea still have certain specificity. This study gives an abundant information of G. conopsea root-associated microbiomes and provides new clues to better understanding the factors affecting the composition and diversity of fungal/bacterial communities associated with orchids. Our results also laying a foundation for harnessing the microbiome for sustainable G. conopsea cultivation. Moreover, these results might be generally applicable to other orchidaceae plants.
Background and Aims
NASH is an increasingly prevalent disease that is the major cause of liver dysfunction. Previous research has indicated that adipose cardiolipin synthase 1 (CRLS1) levels are ...associated with insulin sensitivity; however, the precise roles of CRLS1 and underlying mechanisms involving CRLS1 in the pathological process of NASH have not been elucidated.
Approach and Results
Here, we discovered that CRLS1 was significantly down‐regulated in genetically obese and diet‐induced mice models. In vitro studies demonstrated that overexpression of CRLS1 markedly attenuated hepatic steatosis and inflammation in hepatocytes, whereas short hairpin RNA‐mediated CRLS1 knockdown aggravated these abnormalities. Moreover, high‐fat diet–induced insulin resistance and hepatic steatosis were significantly exacerbated in hepatocyte‐specific Crls1‐knockout (Crls1‐HKO) mice. It is worth noting that Crls1 depletion significantly aggravated high‐fat and high‐cholesterol diet‐induced inflammatory response and fibrosis during NASH development. RNA‐sequencing analysis systematically demonstrated a prominently aggravated lipid metabolism disorder in which inflammation and fibrosis resulted from Crls1 deficiency. Mechanically, activating transcription factor 3 (ATF3) was identified as the key differentially expressed gene in Crls1‐HKO mice through transcriptomic analysis, and our investigation further showed that CRLS1 suppresses ATF3 expression and inhibits its activity in palmitic acid‐stimulated hepatocytes, whereas ATF3 partially reverses lipid accumulation and inflammation inhibited by CRLS1 overexpression under metabolic stress.
Conclusions
In conclusion, CRLS1 ameliorates insulin resistance, hepatic steatosis, inflammation, and fibrosis during the pathological process of NASH by inhibiting the expression and activity of ATF3.
Polyphyllin VII (PP7), a pennogenyl saponin isolated from Rhizoma Paridis, exhibited strong anticancer activities in various cancer types. Previous studies found that PP7 induced apoptotic cell death ...in human hepatoblastoma cancer (HepG2) cells. In the present study, we investigated whether PP7 could induce autophagy and its role in PP7-induced cell death, and elucidated its mechanisms. PP7 induced a robust autophagy in HepG2 cells as demonstrated by the conversion of LC3B-I to LC3B-II, degradation of P62, formation of punctate LC3-positive structures, and autophagic vacuoles tested by western blot analysis or InCell 2000 confocal microscope. Inhibition of autophagy by treating cells with autophagy inhibitor (chloroquine) abolished the cell death caused by PP7, indicating that PP7 induced an autophagic cell death in HepG2 cells. C-Jun N-terminal kinase (JNK) was activated after treatment with PP7 and pretreatment with SP600125, a JNK inhibitor, reversed PP7-induced autophagy and cell death, suggesting that JNK plays a critical role in autophagy caused by PP7. Furthermore, our study demonstrated that PP7 increased the phosphorylation of AMPK and Bcl-2, and inhibited the phosphorylation of PI3K, AKT and mTOR, suggesting their roles in the PP7-induced autophagy. This is the first report that PP7 induces an autophagic cell death in HepG2 cells via inhibition of PI3K/AKT/mTOR, and activation of JNK pathway, which induces phosphorylation of Bcl-2 and dissociation of Beclin-1 from Beclin-1/Bcl-2 complex, leading to induction of autophagy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ulcerative colitis (UC) is an inflammatory bowel disease with a high incidence rate and a difficult treatment regimen. Recently, significant advances in the treatment of intestinal diseases, ...particularly UC, have been made with the use of the drugs baicalin and baicalein, separately or in combination. However, the therapeutic efficacy and mechanism of action of baicalin, baicalein, and their combination therapy, in the treatment of UC has not been fully elucidated.
we constructed a UC rat model that encompassed a variety of complex factors, including a high-sugar and high-fat diet, a high temperature and humidity environment (HTHE), excess drinking, and infection of
. Model rats were then treated with baicalin, baicalein, or a combination of the two.
The results showed significant differences in the therapeutic effects of baicalin, baicalein, and the combination therapy, in the treatment of UC, as well as differences in the inhibition of inflammation
the nuclear factor-κB and MAPK pathways. The rat model of UC was established as described above. Then, the rats were treated for 7 days with baicalin (100 mg kg
), baicalein (100 mg kg
), or both (100 mg kg
, baicalin: baicalein = 4:1/1:1). Clinical symptoms and signs, body temperature, organ indices, histopathology, blood biochemistry, and metabolites were examined to compare treatment effects and indicators of UC. Baicalin, YSR (Young
ratio of baicalin and baicalein), baicalein, and WSR (Withered
ratio of baicalin and baicalein) had significantly different effects in terms of clinical symptoms and signs, body temperature, organ indices, serum inflammatory cytokine levels, blood biochemistry, and histopathology changes in the main organs; YSR exhibited the best treatment effects. LC-MS/MS was used to detect the conversion of baicalin, baicalein, or both, into the six types of metabolites: baicalin, wogonoside, oroxin A, baicalein, wogonin, and oroxylin A. The levels of the six metabolites under the different treatment conditions were significantly different in the large intestine, small intestine, and lungs, but not in the blood. The levels of the six metabolites were significantly different in the large intestine, small intestine, and lung, but not in the serum.
All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in
(Tiaoqin) should be preferred in treatment of UC.
Genistein is one of the main components of soybeans and has been reported to be a potential candidate for the treatment of obesity, cancer, osteoporosis and cardiovascular diseases. Recently, ...genistein has been shown to have therapeutic effects on some chronic skin diseases, but its underlying mechanisms remain unclear. In this study, we evaluated the role of genistein in alleviating squaric acid dibutylester (SADBE)-induced allergic contact dermatitis (ACD) in mice, and elucidated the potential molecular mechanisms in human keratinocyte (HaCaT) cell line. The impacts of genistein on the production of pro-inflammatory chemokines and cytokines including CXCL9, TSLP, TNF-α, IL-1β and IL-6 in the skin and serum of ACD mice were assessed, as well as the phosphorylation of components in the MAPK and JAK-STAT3 signaling pathways in the skin and dorsal root ganglions (DRGs). The results showed that genistein exerted protective effects on skin damage and inflammatory cell infiltration. Moreover, genistein significantly inhibited the increased expressions of pro-inflammatory factors in skin and peripheral blood, and down-regulated the levels of p-ERK, p-p38 and p-STAT3 in skin and DRGs. Furthermore, genistein inhibited the phosphorylation of ERK and STAT3 to downregulate the expression of cytokines and chemokines, and feedback downregulate phospho-p38 in TNF-α/IFN-γ-induced HaCaT cells. The genistein-mediated inhibitory effect on the MAPK pathway can be reversed by siMAP2K2 but not by siMAP2K4. Altogether, our findings demonstrated that genistein exhibits strong antipruritic and anti-inflammatory effects in ACD mice by inhibiting the production of pro-inflammatory cytokines and intracellular MAP2K2/ERK cell signaling, which makes genistein a potentially valuable candidate for the treatment of skin conditions and systemic syndromes in the setting of contact dermatitis.
Genistein, a flavonoid, is one of the main components of soybeans. It was shown to alleviate contact dermatitis through the inhibition of the allergen-induced activation of MAP2K2 in keratinocytes.
Paeonol is a bioactive phenol presents mainly in
Andr. (
),
Pall., and
Thunb. (
), harboring various pharmacological activities including anti-inflammatory, antioxidant, immune regulatory activity ...and reverse chemoresistance. Recent reports revealed paeonol exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis. However, whether paeonol is effective for dry skin disease and its mechanism of action still remain unclear. In this study, we analysed the effects of paeonol on a mouse model of dry skin treated with acetone-ether-water (AEW), which showed impressive activities in reducing scratching behavior and skin inflammation. To elucidate the underlying molecular targets for the anti-pruritic ability of paeonol, we screened the expression of possible chemokine pathways in the spinal cord. The expression of CXCR3 was significantly alleviated by paeonol, which increased greatly in the spinal neurons of AEW mice. In addition, treatment of paeonol significantly inhibited AEW-induced expression of astrocyte activity-dependent genes including
,
and
et al. The inhibitory effects of paeonol on scratching behavior and astrocytic activation in the spinal cord induced by AEW were abolished when CXCR3 was antagonized or genetically ablated. Taken together, our results indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior, and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, which are driven by CXCR3.
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